The first step in the pathway from glucose to glycogen has not
yet been satisfactorily accounted for. The enzyme responsible
for the phosphorylation o f glucose in liver has not been clearly
identified. Qualitatively, Slein, Cori, and Cori (1) postulated a
“glucokinase,” but Crane and Sols (2) reported the identification
o f a hexokinase that apparently had a Michaelis constant (K,,,)
for glucose not as low as those o f the hexokinases o f other tissues.
Quantitatively, the finding by Long (3), in a survey o f glucose
phosphorylation rates by homogenates o f rat organs, that liver
was the least active o f all has been a long standing puzzle. An
important advance was made recently by DiPietro, Sharma,
and Weinhouse (4, 5) when they found that at a high glucose
concentration, the glucose phosphorylation rate o f liver extracts
approaches that required to account for glycogen synthesis from
glucose in normal fed rats. Nevertheless, a major difficulty for
the involvement o f hexokinase as the first step in the pathway o f
glucose to glycogen in liver stems from the finding by Leloir et
al. (6) that the liver UDP-glucose-glycogen glucosyltransferase
(glycogen synthetase) is strongly dependent for activity on a
rather high concentration o f glucose-&P, a strong inhibitor o f
animal tissue hexokinases (2). Because o f these opposing ef fects
o f glucose-6-P, hexokinase and glycogen synthetase would not be
able to work efficiently in sequence. Figueroa, Pfeifer, and
Niemeyer (7) have recently raised doubts as to whether glucose-
6-P is a necessary step in the synthesis o f glycogen from glucose
in liver.
We report h